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2016 ; 44
(9
): 2707-23
Nephropedia Template TP
gab.com Text
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Valve Interstitial Cells Act in a Pericyte Manner Promoting Angiogensis and
Invasion by Valve Endothelial Cells
#MMPMID26905695
Arevalos CA
; Berg JM
; Nguyen JM
; Godfrey EL
; Iriondo C
; Grande-Allen KJ
Ann Biomed Eng
2016[Sep]; 44
(9
): 2707-23
PMID26905695
show ga
Neovascularization is an understudied aspect of calcific aortic valve disease
(CAVD). Within diseased valves, cells along the neovessels' periphery stain for
pericyte markers, but it is unclear whether valvular interstitial cells (VICs)
can demonstrate a pericyte-like phenotype. This investigation examined the
perivascular potential of VICs to regulate valve endothelial cell (VEC)
organization and explored the role of Angiopoeitin1-Tie2 signaling in this
process. Porcine VECs and VICs were fluorescently tracked and co-cultured in
Matrigel over 7 days. VICs regulated early VEC network organization in a
ROCK-dependent manner, then guided later VEC network contraction through
chemoattraction. Unlike vascular control cells, the valve cell cultures
ultimately formed invasive spheroids with 3D angiogenic-like sprouts. VECs
co-cultured with VICs displayed significantly more invasion than VECs alone; with
VICs generally leading and wrapping around VEC invasive sprouts. Lastly,
Angiopoietin1-Tie2 signaling was found to regulate valve cell organization during
VEC/VIC spheroid formation and invasion. VICs demonstrated pericyte-like
behaviors toward VECs throughout sustained co-culture. The change from a
vasculogenic network to an invasive sprouting spheroid suggests that both cell
types undergo phenotypic changes during long-term culture in the model angiogenic
environment. Valve cells organizing into spheroids and undergoing 3D invasion of
Matrigel demonstrated several typical angiogenic-like phenotypes dependent on
basal levels of Angiopoeitin1-Tie2 signaling and ROCK activation. These results
suggest that the ectopic sustained angiogenic environment during the early stages
of valve disease promotes organized activity by both VECs and VICs, contributing
to neovessel formation and the progression of CAVD.